ausblenden:
Schlagwörter:
Basic-Leucine Zipper Transcription Factors/*genetics; Burkitt Lymphoma/*genetics; Cell Line, Tumor; Chromosomes, Human, Pair 20/*genetics; Chromosomes, Human, Pair 6/*genetics; Humans; Oncogene Proteins, Fusion/*genetics; Translocation, Genetic/*genetics; bcl-X Protein/*genetics
Zusammenfassung:
Abnormalities of the long arm of chromosome 6 are a common feature in various B-cell malignancies. In most cases, the genes involved have not yet been clearly identified. We have molecularly characterized the recently established Burkitt lymphoma cell line BLUE-1 that carries a t(6;20)(q15;q11.2) rearrangement in addition to the typical t(8;14) with MYC-IGH fusion. To identify the gene loci involved on both chromosomes we applied a sequential BAC clone mapping strategy. By using RT-PCR we were finally able to detect a chimeric mRNA transcript showing a fusion of the first (non-coding) exon of BACH2 (BTB and CNC homology 1, basic leucine zipper transcription factor 2) on 6q15 to the second exon of BCL2L1 (BCL-X) on 20q11. Various fusion transcripts were detected for different BCL2L1 (BCL-XL) isoforms. The fusion ultimately results in strong expression of the BCL2L1 (BCL-XL) anti-apoptosis protein, as demonstrated by immunoblotting. This is the first report that shows the involvement of both BCL2L1 and the transcription factor BACH2 in a chromosomal rearrangement. It points to BACH2 as a possibly important target in lymphomas with 6q aberrations, although other genes on 6q are probably also involved in these cases. Moreover, it suggests that members of the BCL2 anti-apoptosis gene family other than BCL2 itself might also be involved in lymphoma.
